Introduction: The long term goal of this research is the development of a rapid, reliable diagnostic system for the identification of viruses and bacteria that is suitable for use in point-of-care facilities, as well as in the field for use during times of natural or intentionally caused epidemics. The feasibility of this goal will be demonstrated in the proposed research by the development of immunoassays for West Nile Virus (WNV) and antibodies to WNV, as well as a solution RNA hybridization assay for WNV. In each case, development of the WNV assay will be followed by development of a corresponding assay for St. Louis encephelitis (SLE), which can be commonly be confused for WNV. Finally, simultaneous assays for WNV and SLE will be developed that should allow a user to distinguish between these two types of infection with a very high level of confidence. These simultaneous assays will serve as a model for other diseases that display clinically similar characteristics, such as foot and mouth disease (FMD) and the less worrisome vesicular stomatitis virus (VSV). The assays will rely on surface enhanced Raman scattering (SERS) spectroscopy. While SERS is best known for its extremely high sensitivity, its greatest advantage over other detection methods may be the fact that it is only substances that are localized near a silver or gold surface that are subject to the signal enhancing effects of the metal, allowing assays to be performed without the time-consuming and inconvenient wash steps that are characteristic of most other assay methods. Project interactions: This project will involve a close collaboration between three organizations. CC Technology will provide expertise in SERS assay development, as well as design an instrument for use in the assays that is simple to use by novices. The organic synthesis for the production of Raman tags will be carried out at the University of Wyoming. ABADRL will produce appropriate viruses, antibodies, and nucleic acid tags, and will collaborate in assay development in their BS3 facility.